Cariprazine, A Broad-Spectrum Antipsychotic for the Treatment of Schizophrenia: Pharmacology, Efficacy, and Safety

Abstract

Schizophrenia is characterized by positive, negative, cognitive, and affective symptoms. Antipsychotic medications, which work by blocking the dopamine D 2 receptor, are the foundation of pharmacotherapy for schizophrenia to control positive symptoms. Cariprazine is a dopamine D 3 receptor-preferring D 3 /D 2 partial agonist antipsychotic that is approved for the treatment of schizophrenia (USA and European Union [EU]) and manic and depressive episodes associated with bipolar I disorder (USA). Partial agonist agents have a lower intrinsic activity at receptors than full agonists, so they act as either functional agonists or functional antagonists depending on the surrounding neurotransmitter environment. Beyond efficacy against positive symptoms, the unique D 3 -preferring partial agonist pharmacology of cariprazine suggests potential advantages against negative symptoms, and cognitive and functional impairment, which are challenging to treat. The efficacy and safety of cariprazine in adult patients with schizophrenia have been demonstrated in four short-term randomized, double-blind, placebo-controlled clinical trials, two long-term open-label studies, one relapse prevention study, and one prospective negative symptom study versus the active comparator risperidone. Additional post hoc investigations have supported efficacy across individual symptoms and domains in schizophrenia, as well as in diverse areas of interest including cognition, functioning, negative symptoms, hostility, and global well-being. This comprehensive review of cariprazine summarizes its pharmacologic profile, clinical trial evidence, and post hoc investigations. Collective evidence suggests that the pharmacology of cariprazine may offer broad-spectrum efficacy advantages for patients with schizophrenia, including effects against difficult-to-treat negative and cognitive symptoms, as well as functional improvements. Cariprazine was generally safe and well tolerated in patients with short-and long-term exposure and no new safety concerns were associated with longerduration treatment. Trial registration ClinicalTrials.gov identifiers,

Real-Life Clinical Experience With Cariprazine: A Systematic Review of Case Studies

“…Psychosocial functioning remains one of biggest causes of disability in patients with serious mental illness ( 80 ). Patients have severe social and occupational dysfunctions, difficulty attending to everyday tasks due to clinical symptoms (especially negative, affective and cognitive) or comorbid conditions, which have detrimental effects on their quality of life—yet, it remains a large unmet need ( 81 ). Furthermore, its evaluation is not standardized, as there is no consensus definition of psychosocial functioning ( 82 ).…”

Cariprazine in the Treatment of Bipolar Disorder: Within and Beyond Clinical Trials

“…Cariprazine is an oral medication that is dosed once-daily, with or without food ( 27 ). Following oral administration, cariprazine is rapidly absorbed and reaches peak concentrations within 3–5 h ( 28 ).…”

“…If cariprazine is used in conjunction with carbamazepine, clinicians need to be aware of the potential reduction in cariprazine levels given that carbamazepine is a potent CYP3A4 inducer; hence, the dose of cariprazine may need to be adjusted accordingly to achieve the desired clinical outcomes. The dose of cariprazine should be reduced by 50% when administered concurrently with strong CYP3A4 inhibitors ( 27 ).…”

Reducing Addiction in Bipolar Disorder via Hacking the Dopaminergic System

“…Brexpiprazole studies in bipolar mania were unsuccessful ( 53 ), and, following a positive pilot trial ( 54 ), a RCT in bipolar depression is ongoing ( 55 ). Human PET studies with cariprazine ( 56 , 57 ), aripiprazole ( 58 ), and brexpiprazole ( 58 ) have pointed to the difference potentially explaining these findings: while all three compounds were able to occupy the D 2 receptors in the brain, only cariprazine was able to sufficiently occupy the D 3 receptors as well [( 59 ); Figure 1 ]. Additionally, a clinical trial has been initiated to further study the dopamine D3 receptor occupancy of cariprazine (1.5 vs. 3 mg/day) in patients with unmedicated bipolar depression ( 60 ).…”